The research proposed in this new application will extend our knowledge of a normal human serum protein, P-component of amyloid (SAP). Preliminary studies by the applicant will be pursued to characterize by physicochemical criteria (eg. pH, ionic strength, time, temperature, Ca++ and ligand concentration) the association and dissociation phases of the binding reaction between SAP and ligands (zymosan, Candida and E. coli). SAP will be measured by an immunonephelometric (laser) assay (INT-SAP assay) which already has been developed by the applicant and which employs unlabeled monospecific rabbit anti SAP. For some studies, purified radiolabeled 125-I SAP will serve as tracer. Antibodies (anti SAP) and polysaccharide reagents will be tested for modulation of the SAP-ligand interaction. A biological role for SAP in host defense might be found by examining mixtures of SAP-ligand complexes (zymosan, Candida and E. coli) and polymorphonuclear leukocytes; adherence, phagocytosis and lysosomal enzyme release will be studied. The present proposal is aimed at exploring the potential function of SAP in physiology and pathophysiological conditions. SAP is a 9.5S, 233,000-dalton, alpha-1 glycoprotein. Ten like subunits form a dimer of pentagonal rings. SAP is present in plasma (40 ug/ml), fibroblasts and, purportedly, basement membrane (base mem.). It is not an acute phase reactant and sex hormones may control its metabolism. Analogues are found in other species. SAP binds to ligands via a Ca++-dependent, nonenzymatic reaction. On this basis it is purified on Sepharose and adsorbed onto amyloid deposits in vivo. In preliminary studies, SAP bound zymosan (yeast cell wall) and Candida and E. coli, pathogens known to induce secondary amyloidosis: it was low in some IgA myeloma sera and accumulated in base mem. in some dermatoses. SAP may function as a primordial immunological surveillance system which recognizes glycosyl residues on microbes (Candida, E. coli), tumors, damaged cells and protein (amyloid, base mem., allergens). Lectin-ligand interaction may induce agglutination with attendant biological sequela. The long-term aim is to investigate preliminary data to elucidate a role for SAP in host defense, the mechanism(s) of SAP abnormality in disease and a relationship between SAP and immunoglobulins, another important endogenous carbohydrate recognition system in man.